Catatonia in Dementia: A Systematic Review of Case Reports and Case Series.

BACKGROUND: Catatonia is a neuropsychiatric syndrome characterized by motor, behavioral, and autonomic abnormalities. It is often underdiagnosed in geriatric patients with dementia despite established diagnostic criteria and treatment options. OBJECTIVE: This systematic review investigates catatonia in the elderly, particularly those with dementia, to examine their clinical presentation, treatment response, and prognosis compared to elderly patients without dementia. METHODS: We comprehensively searched MEDLINE and EMBASE, including case reports and series on catatonia in elderly patients. Reviewers independently performed data extraction and quality assessments. Statistical significance was set at a p value ≤0.05, and a multivariate logistic regression model was used to analyze differences between patients with and without dementia. RESULTS: Our review included 182 articles with 225 cases. We found no significant differences in the clinical presentation of catatonia between patients with and without dementia, with both groups commonly exhibiting the hypokinetic variant. However, patients with dementia were more frequently treated with NMDA receptor antagonists (OR: 3.27; CI: 1.05-10.11; p = 0.040) and had a lower complete response rate to treatment (OR: 0.37; CI: 0.19-0.75; p = 0.006). Patients with dementia also exhibited fewer acute medical conditions (OR: 0.17; CI: 0.05-0.65; p = 0.009). CONCLUSIONS: Catatonia in dementia does not have a different syndromic presentation. However, the diagnosis of dementia leads to varying preferences regarding the choice of symptomatic therapy and seems to be a predictor of a poorer therapeutic response. Actively treating catatonia, particularly in patients with dementia, addressing the characteristics of these patients is of paramount importance.

Noninvasive brain stimulation for behavioural and psychological symptoms of dementia: A systematic review and meta-analysis.

BACKGROUND: Pharmacological and conventional nonpharmacological treatments for behavioural and psychological symptoms of dementia (BPSD) have only modest efficacy. Furthermore, pharmacotherapy carries the risk of important side effects. Noninvasive brain stimulation (repetitive transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS)) are valuable and safe for cognitive function in Alzheimer disease (AD). However, there have been few studies, and there is no consensus, regarding the use of these techniques to treat BPSD. METHODS: We performed a systematic review of the literature and meta-analysis of studies reporting the effect of rTMS or tDCS on BPSD. RESULTS: Seven articles were included: five randomized, controlled clinical trials and two open-label clinical trials. Five studies investigated the effects of rTMS and two the effects of tDCS. Both studies using tDCS reported no evidence of efficacy on BPSD, while two of the three RCTs using rTMS found statistically significant benefits. In an exploratory meta-analysis with four of the RCT studies, we did not find evidence of efficacy of noninvasive brain stimulation techniques, with an overall effect of -0.02 (95% CI = -0.90, 0.94; I2  = 85%). However, when we used only the data from the studies that applied rTMS, we found a positive effect on BPSD, with an overall effect of -0.58 (95% CI = -1.02, -0.14; I2  = 0%). With regards to the adverse effects reported, these were mild and not clinically relevant. CONCLUSIONS: Our results establish a tendency for efficacy of rTMS protocols on BPSD, while corroborating their safety and tolerability, suggesting the need for further research.

TBK1 Mutation Spectrum in an Extended European Patient Cohort with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2,538 patients with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein-truncating mutations by measuring loss of RNA expression. Functional effect of in-frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFκB-induced luciferase reporter assay and measuring phosphorylated TBK1. The protein-truncating mutations led to the loss of transcript through nonsense-mediated mRNA decay. For the in-frame amino acid deletions, we demonstrated loss of TBK1 or phosphorylated TBK1 protein. An important fraction of the missense mutations compromised NFκB activation indicating that at least some functions of TBK1 are lost. Although missense mutations were also present in controls, over three times more mutations affecting TBK1 functioning were found in the mutation fraction observed in patients only, suggesting high-risk alleles (P = 0.03). Total mutation frequency for confirmed TBK1 LoF mutations in the European cohort was 0.7%, with frequencies in the clinical subgroups of 0.4% in FTD, 1.3% in ALS, and 3.6% in FTD-ALS.

COVID-19-related consultation-liaison (CL) mental health services in general hospitals: A perspective from Europe and beyond.

OBJECTIVE: The COVID-19 pandemic posed new challenges for integrated health care worldwide. Our study aimed to describe newly implemented structures and procedures of psychosocial consultation and liaison (CL) services in Europe and beyond, and to highlight emerging needs for co-operation. METHODS: Cross-sectional online survey from June to October 2021, using a self-developed 25-item questionnaire in four language versions (English, French, Italian, German). Dissemination was via national professional societies, working groups, and heads of CL services. RESULTS: Of the participating 259 CL services from Europe, Iran, and parts of Canada, 222 reported COVID-19 related psychosocial care (COVID-psyCare) in their hospital. Among these, 86.5% indicated that specific COVID-psyCare co-operation structures had been established. 50.8% provided specific COVID-psyCare for patients, 38.2% for relatives, and 77.0% for staff. Over half of the time resources were invested for patients. About a quarter of the time was used for staff, and these interventions, typically associated with the liaison function of CL services, were reported as most useful. Concerning emerging needs, 58.1% of the CL services providing COVID-psyCare expressed wishes for mutual information exchange and support, and 64.0% suggested specific changes or improvements that they considered essential for the future. CONCLUSION: Over 80% of participating CL services established specific structures to provide COVID-psyCare for patients, their relatives, or staff. Mostly, resources were committed to patient care and specific interventions were largely implemented for staff support. Future development of COVID-psyCare warrants intensified intra- and inter-institutional exchange and co-operation.

Clinical and therapeutic characterization of a Portuguese sample of patients with schizophrenia.

INTRODUCTION: The development of Mental Health policies for psychiatric disorders should be driven by a correct knowledge of the socio-demographic, clinical and therapeutic realities of the disease. There is paucity of detailed studies in the Portuguese population that does not allow a direct comparation with other European countries. The objective of the present study is to characterize the sociodemograhic and clinical characteristics of schizophrenia patients in Portugal and the therapeutic patterns. METHODS: This multicentric, cross sectional, non interventional study was designed to describe the demographic and clinical data of patients with schizophrenia (n=474), and also the demographic and professional characteristics of their treating psychiatrists. RESULTS: The most frequent diagnosis found was paranoid schizophrenia (54%), with comorbid psychiatric conditions in 39,7% and somatic diseases in 28.4% of the patients. About half the patients were on second generation antipsychotics (SGS) as principal therapy, although haloperidol has been the most frequent drug prescribed as so (35.9 %). 59.51 % of the patients were on antipsychotic monotherapy, and 45% on a depot formulation. Antipsychotic dose vary widely, and they are quite often prescribed on off label doses. DISCUSSION: Our sample is similar to others found in naturalistic studies, however slightly different from clinical trials. In general, patients with schizophrenia tend to be treated with SGA, although have a higher chance to be on a long-term formulation and to be on polytherapy than in other studies. Somatic diseases are maybe under diagnosed and are undertreated.

Memory awareness in patients with Major Depressive Disorder.

BACKGROUND: Subjective Memory Complaints (SMC) along with cognitive deficits are frequently observed in patients with Major Depressive Disorder (MDD). The relationship between SMC and objective memory performance in patients with MDD was evaluated, in comparison with patients with Mild Cognitive Impairment due to Alzheimer's Disease (MCI-AD) and healthy controls (HC). METHODS: Patients with MDD (n = 47), MCI-AD (n = 43) and HC (n = 45) were assessed with a self-report memory complaints scale (SMCS) and underwent a comprehensive clinical and neuropsychological assessment. A discrepancy score between the Logical Memory delayed recall and the SMCS total score was calculated as a measure of memory awareness. RESULTS: Patients with MDD (12.5 ± 4.4) and patients with MCI-AD (10.9 ± 4.1) had not significantly different SMCS total scores, whereas HC showed significantly lower scores (4.0 ± 3.0). As much as 74.5% of patients with MDD patients and 65.1% of patients with MCI-AD reported prominent memory complaints, whereas only 4.4% of HC did. Patients with MDD had relatively preserved memory tests, resulting in a higher discrepancy score than both patients with MCI-AD and HC. The SMCS total score correlated positively with depressive symptoms in the 3 groups of participants. CONCLUSIONS: Patients with MDD showed inaccurate memory self-awareness as they under-estimated their memory functioning, a pattern distinct from both patients with MCI-AD and HC.

Sustained NMDA receptor hypofunction impairs brain-derived neurotropic factor signalling in the PFC, but not in the hippocampus, and disturbs PFC-dependent cognition in mice.

BACKGROUND: Cognitive deficits profoundly impact on the quality of life of patients with schizophrenia. Alterations in brain derived neurotrophic factor (BDNF) signalling, which regulates synaptic function through the activation of full-length tropomyosin-related kinase B receptors (TrkB-FL), are implicated in the aetiology of schizophrenia, as is N-methyl-D-aspartate receptor (NMDA-R) hypofunction. However, whether NMDA-R hypofunction contributes to the disrupted BDNF signalling seen in patients remains unknown. AIMS: The purpose of this study was to characterise BDNF signalling and function in a preclinical rodent model relevant to schizophrenia induced by prolonged NMDA-R hypofunction. METHODS: Using the subchronic phencyclidine (PCP) model, we performed electrophysiology approaches, molecular characterisation and behavioural analysis. RESULTS: The data showed that prolonged NMDA-R antagonism, induced by subchronic PCP treatment, impairs long-term potentiation (LTP) and the facilitatory effect of BDNF upon LTP in the medial prefrontal cortex (PFC) of adult mice. Additionally, TrkB-FL receptor expression is decreased in the PFC of these animals. By contrast, these changes were not present in the hippocampus of PCP-treated mice. Moreover, BDNF levels were not altered in the hippocampus or PFC of PCP-treated mice. Interestingly, these observations are paralleled by impaired performance in PFC-dependent cognitive tests in mice treated with PCP. CONCLUSIONS: Overall, these data suggest that NMDA-R hypofunction induces dysfunctional BDNF signalling in the PFC, but not in the hippocampus, which may contribute to the PFC-dependent cognitive deficits seen in the subchronic PCP model. Additionally, these data suggest that targeting BDNF signalling may be a mechanism to improve PFC-dependent cognitive dysfunction in schizophrenia.

[Recommendations about the Use of Psychotropic Medications during the COVID-19 Pandemic]. / Recomendações sobre a Utilização de Fármacos Psicotrópicos durante a Pandemia COVID-19.

INTRODUCTION: The COVID-19 pandemic is a particularly relevant threat to mentally ill patients, and it constitutes a new challenge for health care providers. To the best of our knowledge, there is not any embracing published review about the use of psychotropic drugs during the COVID-19 pandemic. MATERIALS AND METHODS: Non-systematic literature review. A search in the PubMed database was performed, with the terms 'psychotropic drugs', 'COVID-19', 'psychiatry' and 'pandemic'. Consensus and clinical guidelines about psychotropic drugs and COVID-19 approach, published by scientific societies, governmental entities and drug regulatory agencies were included. RESULTS AND DISCUSSION: We present the recommendations about the use of psychotropic drugs during the COVID-19 pandemic, in the outpatient and inpatient settings. The treatment of affective bipolar disorder and schizophrenia have now added increased difficulties. Some psychotropic drugs interfere with the pathophysiology of the novel coronavirus infection and they could interact with the drugs used in the treatment of COVID-19. Some patients will need pharmacological interventions due to the presence of delirium. Smoking cessation changes the serum levels of some psychotropic drugs and may influence their use. CONCLUSION: The COVID-19 pandemic has created new challenges in clinical practice. Psychiatric patients are a vulnerable population and often a careful clinical, laboratorial and electrocardiographic evaluation may be needed, particularly in those diagnosed with COVID-19. The regular treatment of mentally ill patients with COVID-19 presents increased complexity.

Introdução: A pandemia de COVID-19 constitui uma ameaça particularmente relevante para os portadores de doença mental e um novo desafio para os profissionais que os acompanham. Até à data, tanto quanto sabemos, não existe qualquer revisão abrangente publicada relativamente à utilização de fármacos psicotrópicos durante a pandemia COVID-19. Material e Métodos: Revisão não sistemática da literatura. A pesquisa na PubMed foi realizada com os termos 'psychotropic drugs', 'COVID-19', 'psychiatry' e 'pandemic'. Foram incluídos os consensos e as normas publicadas pelas sociedades científicas, entidades governamentais e agências regulamentares de medicamentos. Resultados e Discussão: Apresentam-se recomendações relativamente à utilização de psicofármacos durante a pandemia COVID-19, em contexto de ambulatório e de internamento. O tratamento da perturbação afetiva bipolar e da esquizofrenia tem agora dificuldades acrescidas. Alguns psicofármacos interferem com os mecanismos fisiopatológicos envolvidos na infeção pelo novo coronavírus e têm interações com os fármacos utilizados no tratamento da COVID-19. Em doentes com COVID-19 e com delirium, a utilização de psicofármacos poderá ser necessária. A cessação tabágica altera os níveis séricos de alguns psicofármacos e pode condicionar a sua utilização. Conclusão: A pandemia de COVID-19 coloca novos desafios na prática clínica. Os doentes psiquiátricos constituem uma população vulnerável, sendo frequentemente necessária uma avaliação clínica, laboratorial e eletrocardiográfica cuidadosa, naqueles com o diagnóstico de COVID-19. Os doentes mentais com COVID-19 apresentam uma complexidade acrescida na gestão da sua terapêutica habitual.

[Portuguese Consensus on the Diagnosis and Management of Lewy Body Dementia (PORTUCALE)]. / Consenso Português para o Diagnóstico e Gestão Clínica da Demência com Corpos de Lewy (PORTUCALE).

Lewy body dementia is a common cause of dementia leading to the progressive deterioration of cognitive function and motor skills, behavioral changes, and loss of autonomy, impairing the quality of life of patients and their families. Even though it is the second leading cause of neurodegenerative dementia, diagnosis is still challenging, due to its heterogenous clinical presentation, especially in the early stages of the disease. Accordingly, Lewy body dementia is often misdiagnosed and clinically mismanaged. The lack of diagnostic accuracy has important implications for patients, given their increased susceptibility to the adverse effects of certain drugs, such as antipsychotics, which may worsen some symptoms associated with Lewy body dementia. Therefore, a specialist consensus based on the analysis of the most updated and relevant literature, and on clinical experience, is useful to all professionals involved in the care of these patients. This work aims to inform and provide recommendations about the best diagnostic and therapeutic approaches in Lewy body dementia in Portugal. Moreover, we suggest some strategies in order to raise the awareness of physicians, policy makers, and the society at large regarding this disease.

A demência com corpos de Lewy é uma causa comum de demência, provocando a perda progressiva de funções cognitivas e capacidades motoras, alterações comportamentais, e perda de autonomia, com compromisso da qualidade de vida dos doentes e seus familiares. Apesar de ser a segunda causa mais frequente de demência neurodegenerativa, o diagnóstico mantém-se um desafio, devido à sua apresentação clínica heterogénea, sobretudo nas fases iniciais da doença. Por conseguinte, a demência com corpos de Lewy é frequentemente mal diagnosticada e clinicamente gerida de forma insuficiente. A falta de acuidade diagnóstica tem implicações significativas para os doentes, dada a maior suscetibilidade aos efeitos adversos de determinados fármacos, tais como os antipsicóticos, que podem agravar alguns sintomas associados à demência com corpos de Lewy. Por conseguinte, um consenso de especialistas, baseado na análise da literatura mais atual e relevante, e na experiência clínica, é útil para todos os profissionais envolvidos no cuidado destes doentes. O objetivo deste trabalho é informar e gerar recomendações acerca das melhores abordagens diagnóstica e terapêutica da demência com corpos de Lewy em Portugal. Além disso, sugerimos estratégias para aumentar a sensibilização dos médicos, dos decisores políticos e da sociedade em geral em relação a esta doença.

The use of laboratory tests in patients with mild cognitive impairment.

Cognitive decline in elderly people can be caused by a specific and treatable metabolic disorder, and the use of laboratory tests is recommended as part of the diagnostic workup of patients with dementia. Patients with mild cognitive impairment (MCI) are commonly investigated by a similar laboratory diagnostic workup, however it is not known whether this clinical practice is justified. In the present study, we compared the frequencies of laboratory abnormalities, and laboratory abnormalities relevant for cognitive impairment, in consecutive patients with MCI or dementia (all types) observed in a memory clinic setting. As much as 55.1% of patients with MCI and 60.0% of patients with dementia had at least one abnormal laboratory value (a non-significant difference). The most frequent abnormal analysis was the serum cholesterol, that was high in 28.8% of patients with MCI and in 20.4% of patients with dementia. It was possible to detect, both in patients with MCI (1.5% and in patients with dementia (3.5%, a non-significant difference), abnormal metabolic values, indicating poorly controlled diabetes, renal failure, hyponatremia, folate or vitamin B12 deficiency and hyperthyroidism, which correction led to clinical improvement. The majority (62.5% of these alterations were previously unknown. These findings give support to the use of the laboratory diagnostic workup of dementia in patients with mild cognitive impairment.

Depression with melancholic features is associated with higher long-term risk for dementia.

BACKGROUND: Depression has been reported to increase the risk of subsequently developing dementia, but the nature of this relation remains to be elucidated. Depression can be a prodrome/manifestation of dementia or an early risk factor, and the effect may differ according to depression subtypes. Our aim was to study the association between early-onset depression and different depression subtypes, and the later occurrence of dementia. METHODS: We conducted a cohort study including 322 subjects with depression, recruited between 1977 and 1984. A comparison cohort (non-exposed) was recruited retrospectively, to include 322 subjects admitted at the same hospital for routine surgery (appendicectomy or cholecystectomy), at the same period as the depressed cohort. Subjects were contacted again between 2009 and 2014, to assess their dementia status. We computed the risk for dementia in subjects with early onset depression and quantified the association between different depression subtypes (namely melancholic, anxious, and psychotic) and dementia. RESULTS: The odds of dementia were increased by 2.90 times (95% C.I. 1.61-5.21; p<0.0001) for the depressed cohort when compared to the surgical cohort. When the analysis was restricted to patients younger than 45 years old at baseline, the odds for dementia in the depressed cohort were also significantly higher when compared to the surgical cohort (8.53; 95% C.I. 2.40-30.16). In the multivariate Cox analysis, subjects having depression with melancholic features had an increased risk for developing dementia compared to those without melancholic features (HR=3.64; 95% C.I. 1.78-11.26; p=0.025). LIMITATIONS: About 59% of the participants with depression and 53% of those non-exposed were lost during follow up. The inclusion of biological biomarkers would strengthen the results. The sample included a low number of bipolar patients. CONCLUSIONS: These results support depression as an early risk factor for dementia. Depression with melancholic features was found as an important risk factor for dementia, playing a main role in the relation between these disorders.

Caracterización clínica y terapéutica de un muestreo portugués de pacientes con esquizofrenia / Clinical and therapeutic characterization of a portuguese sample of patients with schizophrenia

Introducción. El desarrollo de las políticas de salud mental sobre trastornos psiquiátricos graves debe llevarse a cabo con un conocimiento adecuado de las realidades socio-demográficas, y clínicas de los padrones de prescripción. En Portugal, los estudios epidemiológicos no tienen un nivel de detalle que haga posible una comprensión profunda de este fenómeno. En la población portuguesa que sufre esquizofrenia hay una carencia de estudios en profundidad que limitan su comparación con otros países europeos. Este estudio ha sido diseñado con el objetivo principal de conocer la práctica clínica habitual y las características de la esquizofrenia en Portugal. Método. Se trata de un estudio observacional, descriptivo, transversal y multicéntrico, con datos recogidos en la práctica clínica corriente. Se han analizado un total de 474 pacientes. Resultados. El diagnóstico más frecuente la esquizofrenia paranoide (54%), de severidad moderada, con frecuentes complicaciones psiquiátricas (39,7%) y somáticas (28,4%). El 48,6% de los pacientes presentaban consumo de drogas. Aproximadamente la mitad de los pacientes tomaban antipsicóticos atípicos como tratamiento principal, aunque el haloperidol fue el medicamento prescrito con más frecuencia (35,9%). El 59,51% de los pacientes estaban siendo tratados en monoterapia antipsicótica y el 45% con una formulación de larga duración inyectable. Las dosis de los antipsicóticos eran muy variables y con frecuencia fuera de la indicación autorizada. El 37,9% de los pacientes tenían terapia concomitante no farmacológica. Conclusiones. Los pacientes presentan características sociodemográficas similares a las de otros ensayos clínicos naturalistas, pero diferentes de los ensayos clínicos con fármacos. En general, los pacientes se tratan con antipsicóticos atípicos, aunque un gran porcentaje prosigue con formulaciones de liberación lenta en terapia de combinación con dos o más antipsicóticos, en cifras mayores que en otros estudios similares. Las enfermedades somáticas quizás se infradiagnostica no se tratan de manera insuficiente (AU)

Introduction. The development of Mental Health policies for psychiatric disorders should be driven by a correct knowledge of the socio-demographic, clinical and therapeutic realities of the disease. There is paucity of detailed studies in the Portuguese population that does not allow a direct comparation with other European countries. The objective of the present study is to characterize the sociodemograhic and clinical characteristics of schizophrenia patients in Portugal and the therapeutic patterns. Methods. This multicentric, cross sectional, non interventional study was designed to describe the demographic and clinical data of patients with schizophrenia (n=474), and also the demographic and professional characteristics of their treating psychiatrists. Results. The most frequent diagnosis found was paranoid schizophrenia (54%), with comorbid psychiatric conditions in 39,7% and somatic diseases in 28.4% of the patients. About half the patients were on second generation antipsychotics (SGS) as principal therapy, although haloperidol has been the most frequent drug prescribed as so (35.9 %). 59.51 % of the patients were on antipsychotic monotherapy, and 45% on a depot formulation. Antipsychotic dose vary widely, and they are quite often prescribed on off label doses. Discussion. Our sample is similar to others found in naturalistic studies, however slightly different from clinical trials. In general, patients with schizophrenia tend to be treated with SGA, although have a higher chance to be on a long-term formulation and to be on polytherapy than in other studies. Somatic diseases are maybe under diagnosed and are undertreated (AU)